Experiments will be done to inhibit lysosomal cathepsins D and B1 of liver in order to determine the function each of these enzymes has in digesting phagocytized 125I-labeled asialo-fetuin. The two bacterial peptides, pepstatin and leupeptin, which are specific inhibitors of the two respective cathepsins will be added to the perfusage being circulated through an isolated rat liver. At later times 125I-asialo-fetuin will be injected into this system and the rates of liver uptake and subsequent proteolysis of the glycoprotein will be measured. These values will be compared to those obtained using a liver not treated with pepstatin or leupeptin. In other studies liposomes will be prepared according to published methods using purified lipids. An attempt will then be made to incorporate an asialo-glycoprotein into the outer surface of these vesicles in order to provide them with the biological signal for hepatocyte heterophagy. The proteins to be used for this purpose are asialo-glycophorin isolated from human red cells ghost and asialo-fetuin. Such liposomes will eventually be used to direct either inhibitors, activators or hydrolases themselves into hepatocyte lysosomes.